11-85882657-C-A

Position:

• chr11-85882657-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286159.2(CCDC83):​c.325C>A​(p.Gln109Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC83 NM_001286159.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

Genes affected

CCDC83 (HGNC:28535): (coiled-coil domain containing 83)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11490622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2	c.325C>A	p.Gln109Lys	missense_variant	4/11	ENST00000342404.8	NP_001273088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC83	ENST00000342404.8	c.325C>A	p.Gln109Lys	missense_variant	4/11	1	NM_001286159.2	ENSP00000344512.3
CCDC83	ENST00000526729.1	c.208C>A	p.Gln70Lys	missense_variant	2/8	1		ENSP00000434373.1
CCDC83	ENST00000280245.8	c.325C>A	p.Gln109Lys	missense_variant	4/12	2		ENSP00000280245.4
CCDC83	ENST00000529676.2	n.86+9362C>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460802 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.325C>A (p.Q109K) alteration is located in exon 4 (coding exon 3) of the CCDC83 gene. This alteration results from a C to A substitution at nucleotide position 325, causing the glutamine (Q) at amino acid position 109 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0081	.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.13
Sift	Benign	0.31	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.48	P;D
Vest4		0.22
MutPred		0.36		Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP		0.15
MPC		0.026
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2093307039; hg19: chr11-85593700; COSMIC: COSV99721965;